ENST00000355690.8:c.10+4478A>G

Variant names:

• chr12-9955834-A-G
• rs676397
• ENST00000355690.8:c.10+4478A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000355690.8(CLEC12A):​c.10+4478A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,232 control chromosomes in the GnomAD database, including 57,912 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (57912 hom., cov: 33)
• Consequence: CLEC12A ENST00000355690.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 3 publications found

Genes affected

CLEC12A (HGNC:31713): (C-type lectin domain family 12 member A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signaling, glycoprotein turnover, and roles in inflammation and immune response. The protein encoded by this gene is a negative regulator of granulocyte and monocyte function. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. This gene is closely linked to other CTL/CTLD superfamily members in the natural killer gene complex region on chromosome 12p13. [provided by RefSeq, May 2011]

LOC124902874 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000355690.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC12A	NM_001207010.2		c.10+4478A>G		intron	N/A	NP_001193939.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC12A	ENST00000355690.8	TSL:1	c.10+4478A>G		intron	N/A	ENSP00000347916.4

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132402 AN: 152114 Hom.: 57866 Cov.: 33

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.944

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.880

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.870 AC: 132504 AN: 152232 Hom.: 57912 Cov.: 33 AF XY: 0.872 AC XY: 64922 AN XY: 74434

African (AFR) AF: 0.795 AC: 32992 AN: 41510

American (AMR) AF: 0.915 AC: 14000 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3142 AN: 3470

East Asian (EAS) AF: 0.823 AC: 4264 AN: 5184

South Asian (SAS) AF: 0.872 AC: 4206 AN: 4826

European-Finnish (FIN) AF: 0.944 AC: 10003 AN: 10596

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.896 AC: 60981 AN: 68034

Other (OTH) AF: 0.880 AC: 1857 AN: 2110

Alfa AF: 0.886 Hom.: 200898

Bravo AF: 0.864

Asia WGS AF: 0.876 AC: 3047 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.47
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs676397; hg19: chr12-10108433;